Affinage

AAMP

Angio-associated migratory cell protein · UniProt Q13685

Length
434 aa
Mass
46.8 kDa
Annotated
2026-04-28
12 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AAMP is a WD40- and immunoglobulin-domain-containing protein that promotes cell migration and angiogenesis by acting as a signaling scaffold for Rho-family GTPases. AAMP stabilizes RhoA by binding it and suppressing SMURF2-mediated ubiquitination and degradation, thereby sustaining RhoA/Rho kinase signaling downstream of VEGF to drive actin stress fiber formation and endothelial tube formation (PMID:26350504, PMID:34901393). AAMP also activates CDC42 by displacing its GAP (ARHGAP1), promoting cellular protrusions and invasion (PMID:33279622), and binds Nod2 through its WD40 domains to modulate NF-κB-mediated innate immune signaling (PMID:19535145). AAMP turnover is itself regulated by ubiquitination, and its levels control endothelial barrier integrity and the stability of both RhoA and RhoB (PMID:39404373).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1996 Medium

    Identification of AAMP as a heparin-binding, immunoglobulin/WD40-domain protein whose antibody blockade inhibits endothelial tube formation established it as a participant in angiogenesis, though no signaling mechanism was known.

    Evidence Biochemical characterization and anti-AAMP antibody blockade of HUVEC tube formation on Matrigel

    PMID:8660919 PMID:8683944

    Open questions at the time
    • Mechanism of action in tube formation undefined
    • Downstream signaling pathway unknown
    • Antibody blockade does not distinguish cell-autonomous from paracrine roles
  2. 1997 Medium

    Demonstration that an AAMP-derived heparin-binding peptide mediates cell surface binding and partially inhibits tumor cell migration linked AAMP's N-terminal domain to cell motility via glycosaminoglycan interactions.

    Evidence Heparin-binding assay, cell clustering, and migration inhibition with peptide variants and heparin competition

    PMID:18634104

    Open questions at the time
    • Full-length protein function not tested in migration
    • Identity of glycosaminoglycan binding partners not resolved
    • In vivo relevance not assessed
  3. 2009 High

    Discovery of AAMP as a direct Nod2-binding partner that modulates NF-κB activation revealed a previously unrecognized role in innate immune signaling, mapping the interaction to AAMP's WD40 domains.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, domain mapping, siRNA knockdown with NF-κB reporter in HEK293T cells

    PMID:19535145

    Open questions at the time
    • Whether AAMP modulates Nod2 signaling in primary immune cells not shown
    • Structural basis of WD40–Nod2 interaction unresolved
    • Relevance to pathogen-triggered innate immunity in vivo unknown
  4. 2015 High

    Placing AAMP upstream of the RhoA/Rho kinase axis in VEGF-stimulated endothelial cells resolved the signaling pathway through which AAMP drives angiogenesis and actin stress fiber formation.

    Evidence siRNA knockdown, antibody blockade, tube formation, aortic ring assay, collagen gel contraction, and actin staining in endothelial cells

    PMID:26350504

    Open questions at the time
    • Direct physical interaction between AAMP and RhoA not yet demonstrated at this stage
    • Whether AAMP acts on other Rho GTPases beyond RhoA was unclear
  5. 2020 Medium

    Identification of AAMP as a CDC42 activator that displaces the GAP ARHGAP1 revealed a second Rho GTPase axis through which AAMP promotes cellular protrusions and invasion.

    Evidence Co-immunoprecipitation, CDC42 activation assay, ARHGAP1 displacement, siRNA and overexpression in NSCLC cells

    PMID:33279622

    Open questions at the time
    • Single lab; independent replication pending
    • Whether CDC42 and RhoA axes operate simultaneously or in distinct contexts not defined
    • Structural basis for ARHGAP1 displacement unknown
  6. 2021 High

    Demonstration that AAMP physically binds RhoA and protects it from SMURF2-mediated ubiquitination and degradation provided the direct molecular mechanism underlying AAMP's stabilization of active RhoA.

    Evidence Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, RhoA activity and migration/invasion assays in CRC cells

    PMID:34901393

    Open questions at the time
    • Whether AAMP similarly shields CDC42 from ubiquitin-dependent degradation not tested
    • AAMP-RhoA binding interface not structurally characterized
    • In vivo relevance in tumor models not established
  7. 2022 Medium

    Identification of AAMP as a direct binding partner of the immune checkpoint molecule B7-H3 expanded AAMP's functional repertoire to co-stimulatory immune regulation in cancer.

    Evidence Yeast two-hybrid, mass spectrometry, BiFC, co-immunoprecipitation, T cell proliferation assay

    PMID:35919070

    Open questions at the time
    • Single lab; independent confirmation needed
    • Downstream signaling consequences of AAMP–B7-H3 interaction not mechanistically defined
    • In vivo immunological impact not demonstrated
  8. 2024 Medium

    Revealing that AAMP itself is a ubiquitination substrate whose turnover controls endothelial barrier function — and that AAMP regulates both RhoA and RhoB — closed the feedback loop between AAMP stability and Rho GTPase signaling.

    Evidence Proteomics with E1/Cullin ligase inhibitors, RhoA/RhoB activity and stability assays, co-localization with F-actin and cortactin, endothelial barrier assay

    PMID:39404373

    Open questions at the time
    • Identity of the E3 ligase(s) targeting AAMP for degradation not determined
    • Relative contributions of RhoA vs. RhoB to AAMP-dependent barrier regulation unclear
    • Single study; independent validation needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ligase(s) responsible for AAMP ubiquitination, the structural basis of AAMP's interactions with RhoA, CDC42, and Nod2, and the in vivo consequences of AAMP loss in angiogenesis and immunity remain unresolved.
  • No structural model of AAMP or its complexes exists
  • No genetic animal model phenotype reported
  • Integration of AAMP's Rho GTPase, NF-κB, and B7-H3 functions into a unified physiological model is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 2
Partners
ARHGAP1CD276CDC42NOD2RHOARHOBSMURF2

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 AAMP is a 52 kDa protein containing immunoglobulin-type domains, WD40 repeats, a large acidic region, a potential transmembrane region, serine/threonine phosphorylation sites, and a positively charged amino-terminal region with heparin-binding potential (Kd = 14 pmol). Anti-AAMP antibody inhibits endothelial tube formation on Matrigel, establishing AAMP as a regulator of this process. Biochemical characterization, heparin-binding assay, anti-AAMP antibody blockade of tube formation in HUVEC cultures Laboratory investigation Medium 8683944
1996 AAMP shares a common antigenic epitope (ESESES) with alpha-actinin and a fast skeletal muscle fiber protein, and shows increased expression upon T lymphocyte activation. Polyclonal antibody generation to AAMP-derived peptide P189, immunoblotting, competition studies with peptide variants, thermolysin digestion, immunoperoxidase staining Experimental cell research Medium 8660919
1997 An AAMP-derived peptide (P189) containing a heparin-binding motif near the amino terminus mediates heparin-sensitive cell binding and clustering, and partially inhibits tumor cell migration; cell surface glycosaminoglycans are implicated as the binding moiety. Heparin-binding assay (Kd = 306 pmol), cell binding/clustering assay with peptide variants, heparin competition, electron microscopy Biotechnology and bioengineering Medium 18634104
2009 AAMP was identified as a direct binding partner of Nod2, with an internal AAMP peptide spanning three WD40 domains sufficient for interaction. AAMP modulates Nod2- and Nod1-mediated NF-κB activation, and localizes predominantly to the cytosol in epithelial cells. Yeast two-hybrid screen, co-immunoprecipitation from human cells, overexpression and siRNA knockdown in HEK293T cells with NF-κB reporter assay, immunofluorescence localization Molecular immunology High 19535145
2013 AAMP knockdown via ribozyme transgene reduces cell adhesion and growth of MCF-7 breast cancer cells and suppresses invasion of MDA-MB-231 cells, establishing a role for AAMP in breast cancer cell adhesion and invasion. Hammerhead ribozyme knockdown, in vitro cell adhesion, growth, and invasion assays Anticancer research Medium 23564791
2015 AAMP regulates VEGF-induced endothelial cell migration and angiogenesis through RhoA/Rho kinase signaling; VEGF upregulates AAMP expression and recruits it to cell membrane protrusions. AAMP knockdown reduces actin stress fibers and collagen gel contraction. siRNA knockdown, antibody blockade, tube formation assay, aortic ring assay, collagen gel contraction, actin staining, subcellular localization by imaging Annals of biomedical engineering High 26350504
2020 AAMP interacts with CDC42 and promotes its activation, leading to formation of cellular protrusions in NSCLC cells. AAMP impairs the interaction between ARHGAP1 (a GAP for CDC42) and CDC42, thereby sustaining CDC42 activation and enhancing migration and invasion. Co-immunoprecipitation, CDC42 activation assay, siRNA knockdown, overexpression, cellular protrusion and migration/invasion assays Cancer letters Medium 33279622
2021 AAMP stabilizes RhoA by binding to it and suppressing SMURF2-mediated ubiquitination and degradation of RhoA, resulting in increased active RhoA levels and enhanced CRC cell migration and invasion. Co-immunoprecipitation, ubiquitination assay, AAMP knockdown and overexpression, migration/invasion assays, RhoA activity assay Molecular therapy oncolytics High 34901393
2022 AAMP was identified as a direct binding partner of the co-stimulatory protein B7-H3 in cancer cells, confirmed by bimolecular fluorescence complementation and co-immunoprecipitation, with functional evidence affecting T cell proliferation. Yeast two-hybrid, mass spectrometry screen, bimolecular fluorescence complementation (BiFC), co-immunoprecipitation, 3H-thymidine proliferation assay in Jurkat T cells Neuro-oncology advances Medium 35919070
2024 AAMP is a negative regulator of endothelial barrier function whose stability is controlled by ubiquitination; AAMP regulates the stability and activity of both RhoA and RhoB, and colocalizes with F-actin and cortactin at membrane ruffles, implicating it in F-actin dynamics. Proteomics screen following E1 ligase inhibitor (MLN7243) and Cullin E3 ligase inhibitor (MLN4924) treatment, RhoA/RhoB activity and stability assays, co-localization imaging (F-actin, cortactin), endothelial barrier function assay in primary human endothelial cells Cells Medium 39404373

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 A function for AAMP in Nod2-mediated NF-kappaB activation. Molecular immunology 30 19535145
2015 AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling. Annals of biomedical engineering 22 26350504
1996 AAMP, a conserved protein with immunoglobulin and WD40 domains, regulates endothelial tube formation in vitro. Laboratory investigation; a journal of technical methods and pathology 20 8683944
2021 AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA. Molecular therapy oncolytics 18 34901393
2016 The concept of allergen-associated molecular patterns (AAMP). Current opinion in immunology 16 27619413
2020 Angio-associated migratory cell protein (AAMP) interacts with cell division cycle 42 (CDC42) and enhances migration and invasion in human non-small cell lung cancer cells. Cancer letters 14 33279622
2013 The impact of angio-associated migratory cell protein (AAMP) on breast cancer cells in vitro and its clinical significance. Anticancer research 13 23564791
2022 AAMP is a binding partner of costimulatory human B7-H3. Neuro-oncology advances 12 35919070
1996 AAMP, a newly identified protein, shares a common epitope with alpha-actinin and a fast skeletal muscle fiber protein. Experimental cell research 12 8660919
2024 AAMP and MTSS1 Are Novel Negative Regulators of Endothelial Barrier Function Identified in a Proteomics Screen. Cells 2 39404373
2023 A crucial exosome-related gene pair (AAMP and ABAT) is associated with inflammatory cells in intervertebral disc degeneration. Frontiers in immunology 2 37122729
1997 The aggregated form of an AAMP derived peptide behaves as a heparin sensitive cell binding agent. Biotechnology and bioengineering 2 18634104